Methotrexate in Early Chikungunya Arthritis: A 6 Month Randomized Controlled Open-label Trial

Objective: Evidence for treating chikungunya arthritis early in the course of illness is scarce. This study assesses the efficacy of Methotrexate in early Chikungunya arthritis. Methods: It is a randomized controlled open-label assessor-blinded trial with a crossover design. Sixty patients with persistent post chikungunya arthritis with at least 3 or more tender or swollen joints (28 joint count) were recruited. MTX arm was given oral Methotrexate and NSAID arm was given NSAIDs (Naproxen 1 gm/day or Etoricoxib 120 mg/day). Patients were followed at 1, 2, 4 and 6 months. After 2 months patients in NSAID arm who have not achieved remission were given MTX. The primary endpoint was remission (no tender or swollen joints by 28 joint count) at 6 months. Secondary endpoints were change in CDAI, Indian HAQ, total steroid use, total NSAID use, and serious adverse effects. Intention to treat analysis was used. Results: TJC, SJC, CDAI and HAQ were matched between two at baseline. Remission was achieved by 28 patients (93%, CI- 78%-98%) in the NSAID arm and 26 patients (86%, CI-70%- 94%) in MTX arm (p=0.18). There was no significant difference in steroid need, change in HAQ, CDAI, TJC or SJC. Those who have not achieved remission had higher disease activity at baseline. Conclusion: A protocol-based approach with steroid and NSAIDs helped to achieve remission in most patients with early subacute phase of post-Chikungunya arthritis and the effect was comparable to that of early initiation of methotrexate.

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Comparison of Tobramycin Pharmacokinetics After Administration by Cris and a Traditional Intravenous Piggyback Infusion

Annals of Pharmacotherapy ◽

10.1177/106002809502900502 ◽

1995 ◽

Vol 29 (5) ◽

pp. 465-469

Author(s):

Vincent F Mauro ◽

Lori R Jacobs ◽

Laurie S Mauro ◽

Rodger D MacArthur ◽

Donald B White

Keyword(s):

Maximum Concentration ◽

Elimination Rate ◽

Random Order ◽

Open Label ◽

Medical College ◽

Primary Endpoints ◽

Significant Difference ◽

Secondary Endpoints ◽

Open Label Trial ◽

Infusion System

Objective: To compare the administration pharmacokinetics of a 30-minute intravenous piggyback (ivpb) infusion of tobramycin with those of controlled-release infusion system (CRIS) using a 20-mL vial at rates of 60 and 120 mL/h. Design: Randomized, controlled, crossover, prospective, open-label trial. Setting: Medical college-affiliated hospital. Participants: Eight healthy volunteer men between the ages of 22 and 24 years weighing between 60 and 90 kg. Interventions: Volunteers received, in random order, tobramycin sulfate 2 mg/kg iv on 3 occasions separated by 1 week. The drug was administered using a 50-mL ivpb infusion at 100 mL/h for 30 minutes, and with the CRIS using a 20-mL vial with flow rates of 60 mL/h for 1 hour (slow) and 120 mL/h for 1 hour (fast). Main Outcome Measures: Primary endpoints were area under the time–concentration curve (AUC), time to reach maximum concentration (tmax), and maximum concentration (Cmax). Secondary endpoints were elimination rate constant (ke), clearance (Cl), and half-life (t1/2). Results: Six volunteers successfully completed the trial. The tmax values observed following fast CRIS and ivpb were 28 ± 8 and 32 ± 4 minutes, respectively, and not significantly different from each other. Both occurred significantly earlier than the tmax associated with slow CRIS (44 ± 7 min). The Cmax values observed following ivpb (11.2 ± 1.5 mg/L) and slow CRIS (10.9 ± 0.9 mg/L) administration were not significantly different from each other, but both were significantly lower than that of fast CRIS (13.4 ± 1.5 mg/L). The AUCs of slow and fast CRIS were 29.8 ± 4.8 and 31.2 ± 3.8 mg/L•h, respectively, and were not significantly different from each other. The AUC of fast CRIS was significantly greater than that observed with ivpb (27.4 ± 4.3 mg/L•h). No significant difference in ke (fast CRIS 0.32 ± 0.03 h-1; slow CRIS 0.33 ± 0.04 h-1; ivpb 0.34 ± 0.0 h-1) was observed among any of the methods. Conclusions: CRIS administration of tobramycin resulted in higher AUCs than did ivpb administration. Compared with ivpb, fast CRIS resulted in a higher Cmax, but the tmax values of fast CRIS and ivpb administration were not statistically different. Compared with ivpb, slow CRIS resulted in a more delayed tmax, but the Cmax values of slow CRIS and ivpb were not statistically different.

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Ten-day bismuth-containing quadruple therapy versus 7-day proton pump inhibitor-clarithromycin containing triple therapy as first-line empirical therapy for the Helicobacter pylori infection in Korea: a randomized open-label trial

BMC Gastroenterology ◽

10.1186/s12876-021-01680-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Young-Il Kim ◽

Jong Yeul Lee ◽

Chan Gyoo Kim ◽

Boram Park ◽

Jin Young Park ◽

...

Keyword(s):

Helicobacter Pylori ◽

Line Treatment ◽

First Line ◽

Open Label ◽

Quadruple Therapy ◽

Intention To Treat ◽

Open Label Trial ◽

H Pylori ◽

Treat Analysis ◽

First Line Treatment

Abstract Background This randomized, open-label trial aimed to compare the efficacy of 10-day bismuth-containing quadruple therapy (BQT) with 7-day proton-pump inhibitor-clarithromycin containing standard triple therapy (STT) as an empirical first-line Helicobacter pylori therapy. Methods Participants with H. pylori infection were randomly assigned to either 10-day BQT (daily doses of bismuth 300 mg, four times; lansoprazole 30 mg, twice; metronidazole 500 mg, three times; and tetracycline 500 mg, four times) or 7-day STT (lansoprazole 30 mg; amoxicillin 1,000 mg; and clarithromycin 500 mg; each given twice daily). Participants who failed initial therapy were crossed over to the alternative treatment regimen. Primary outcome was the eradication rates of first-line treatment by intention-to-treat analysis. Results Study participants (n = 352) were randomized to receive either 10-day BQT (n = 175) or 7-day STT (n = 177). The BQT-group achieved a significantly higher eradication rate than the STT-group in the intention-to-treat analysis (74.3% vs 57.1%, respectively; P = 0.001), modified intention-to-analysis (87.2% [130/149] vs 68.7% [101/147], respectively; P < 0.001) and per-protocol analysis (92.9% [105/113] vs 70.1% [94/134], respectively; P < 0.001). Although there was no serious adverse event, the compliance was lower with BQT than STT as a higher proportion of participants in the BQT-group discontinued therapy because of adverse events than those in the STT-group (23.1% vs 9.1%, respectively; P = 0.001) Conclusions Ten-day BQT had higher eradication rates compared to that of the 7-day STT as an empirical first-line treatment for H. pylori eradication in Korea. Trial registration: ClinicalTrials.gov, NCT02557932. Registered 23 September 2015, https://clinicaltrials.gov/ct2/show/NCT02557932?term=NCT02557932&draw=2&rank=1.

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Daily consumption of fermented soymilk helps to improve facial wrinkles in healthy postmenopausal women in a randomized, parallel-group, open-label trial

Functional Foods in Health and Disease ◽

10.31989/ffhd.v8i2.412 ◽

2018 ◽

Vol 8 (2) ◽

pp. 107 ◽

Cited By ~ 1

Author(s):

Mitsuyoshi Kano ◽

Kazuyoshi Haga ◽

Kouji Miyazaki ◽

Fumiyasu Ishikawa

Keyword(s):

Postmenopausal Women ◽

Maximum Depth ◽

Liquid Chromatography Mass Spectrometry ◽

Daily Consumption ◽

Open Label ◽

Facial Wrinkle ◽

Crow’S Feet ◽

Parallel Group ◽

Secondary Endpoints ◽

Open Label Trial

Background: Soymilk fermented by lactobacilli and/or bifidobacteria is attracting attention due to the excellent bioavailability of its isoflavones. We investigated the effects of fermented soymilk containing high amounts of isoflavone aglycones on facial wrinkles and urinary isoflavones in postmenopausal women in a randomized, parallel-group, open-label trial. Healthy Japanese women were randomly divided into active (n = 44, mean age 56.3 ± 0.5) or control (n = 44, mean age 56.1 ± 0.5) groups, who consumed or did not consume a bottle of soymilk fermented by Bifidobacterium breve strain Yakult and Lactobacillus mali for 8 weeks. Maximum depth of wrinkles around the crow’s feet area and other wrinkle parameters were evaluated as primary and secondary endpoints respectively at weeks 0, 4, and 8 during the consumption period. Urinary isoflavone levels were determined by liquid chromatography-mass spectrometry. Results: The active group demonstrated significant improvements in the maximum depth (p=0.015) and average depth (p=0.04) of wrinkles, and significantly elevated urinary isoflavones (daidzein, genistein, and glycitein; each p < 0.001) compared with the control during the consumption period. No serious adverse effects were recorded.Conclusion: These findings suggest that fermented soymilk taken daily may improve facial wrinkles and elevate urinary isoflavones in healthy postmenopausal women.Key words: postmenopausal women; isoflavone; fermented soymilk; phytoestrogen; facial wrinkle

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TSCQ study: a randomized, controlled, open-label trial of daily trimethoprim-sulfamethoxazole or weekly chloroquine among adults on antiretroviral therapy in Malawi: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-016-1392-3 ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Matthew B. Laurens ◽

Randy G. Mungwira ◽

Osward M. Nyirenda ◽

Titus H. Divala ◽

Maxwell Kanjala ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Antiretroviral Therapy ◽

Study Protocol ◽

Controlled Trial ◽

Open Label ◽

Randomized Controlled ◽

Open Label Trial

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Efficacy and safety of a centrally acting analgesic flupirtine in primary knee osteoarthritis in comparison to tramadol: a randomized controlled trial

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20180484 ◽

2018 ◽

Vol 7 (3) ◽

pp. 381

Author(s):

Tanmoy Kanti Goswami ◽

Pradip Kumar Ghoshal ◽

Avijit Hazra ◽

Asish Biswas

Keyword(s):

Randomized Controlled Trial ◽

Adverse Effects ◽

Controlled Trial ◽

Opioid Analgesics ◽

Womac Score ◽

Open Label ◽

Knee Oa ◽

Randomized Controlled ◽

Significant Difference ◽

Considerable Morbidity

Background: Osteoarthritis (OA) is a chronic, degenerative joint disorder responsible for considerable morbidity, particularly in old age. Flupirtine, a new centrally acting analgesic, is devoid of the adverse effects of NSAIDs and opioid analgesics. In this study author compared the effectiveness and safety of flupirtine with tramadol in knee OA.Methods: An open label, randomized, controlled trial was done with patients of primary knee OA of both sexes, age >50 years. Patients were recruited from Rheumatology OPD of SSKM Hospital. A minimum WOMAC score of 35 was essential for recruitment. Patients with serious comorbidities were excluded. They were treated orally with either flupirtine (100mg thrice daily) or tramadol (50mg thrice daily) for 12 weeks.Results: Ninety patients were recruited and data of 42 on flupirtine and 41 on tramadol were analysed. There was significant improvement in pain, stiffness and physical function compared to baseline in both the groups. However, there was no significant difference between groups at 4, 8 and 12 weeks. Responder rate (50% reduction in pain score from baseline) was 66.67% with flupirtine and 48.78% with tramadol (p = 0.122). Flupirtine caused 4 adverse events compared to 16 with tramadol. However, both the drugs were well-tolerated.Conclusions: The effectiveness of flupirtine in knee OA is comparable to tramadol, while causing minimal adverse effects. Long-term benefits need to be explored.

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Quality of surgical randomized controlled trials in hand surgery: a systematic review

Journal of Hand Surgery (European Volume) ◽

10.1177/1753193418780184 ◽

2018 ◽

Vol 43 (8) ◽

pp. 801-807 ◽

Cited By ~ 5

Author(s):

Chao Long ◽

Heather E. desJardins-Park ◽

Rita Popat ◽

Paige M. Fox

Keyword(s):

Randomized Controlled Trials ◽

Hand Surgery ◽

Controlled Trials ◽

Jadad Score ◽

Surgical Interventions ◽

Intention To Treat ◽

Randomized Controlled ◽

Treat Analysis ◽

Over Time

We assessed the quantity, quality and trends of randomized controlled trials comparing hand surgical interventions. Study characteristics were collected for 125 randomized controlled trials comparing hand surgical interventions. The Jadad scale (0–5), which assesses methodological quality of trials, was calculated. Logistic regressions were conducted to determine associations with the Jadad score. The studies were published between 1981 and 2015, with an increase over time, most often in Journal of Hand Surgery (European). Mean study size was 68 patients. Mean Jadad score was 2.1, without improvement over time. Thirty percent conducted a power analysis and 8% an intention-to-treat analysis. Studies conducted in the United Kingdom and with smaller sample sizes, power analysis and intention-to-treat analysis were associated with a higher Jadad score. The quantity of trials has increased over time while methodological quality has remained low, indicating a need to improve quality of trials in hand surgery literature.

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Abstract 17169: The Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial

Circulation ◽

10.1161/circ.132.suppl_3.17169 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Erin A Bohula ◽

Robert P Giugliano ◽

Christian T Ruff ◽

Julia F Kuder ◽

Sabina A Murphy ◽

...

Keyword(s):

Renal Function ◽

Clinical Outcome ◽

Factor Xa ◽

Intention To Treat ◽

Significant Difference ◽

Prevention Of Thromboembolic Events ◽

Treatment Analysis ◽

Net Clinical Benefit ◽

The Impact ◽

Treat Analysis

Background: Edoxaban (edox), an oral factor Xa inhibitor with 50% renal clearance, was non-inferior to warfarin for prevention of thromboembolic events and significantly reduced bleeding in pts with AF. However, a detailed analysis of the impact of creatinine clearance (CrCl) on clinical outcomes with edox has not been described. Purpose: We evaluated the safety, efficacy and net clinical outcome of edox vs warfarin (warf) across the range of baseline CrCl in the ENGAGE AF-TIMI 48 trial. Methods: 14,071 AF pts at moderate-to-high risk of stroke were randomized to edox 60mg QD or warf. Severe renal dysfunction (CrCl<30ml/min) was exclusionary and a CrCl 30-50 resulted in a 50% dose reduction of edox (30mg QD). Endpoints of stroke or systemic embolism (SSE), ISTH major bleeding (MB) and the primary net clinical outcome of SSE/MB and all-cause mortality (ACM) were evaluated by intention-to-treat analysis by the pre-specified singular CrCl cutpoint of 50ml/min and additional exploratory cutpoints. Results: The relative risk of SSE with edox vs warf in the pre-specified analysis in those with CrCl≤50 (HR 0.87, 0.65-1.18) was similar to those with CrCl>50 (HR 0.87, 0.72-1.04; p-int=0.94). Evaluation by more granular, exploratory cutpoints demonstrated higher rates of SSE (Fig 1a; p-int<0.001) and ischemic stroke (p-int=0.05) with edox vs warf in the upper range of CrCl, but lower rates of bleeding were observed at all levels of CrCl with edox (Fig 1a; p-int=0.39). For the net clinical outcome (SSE/MB/ACM), there was no significant difference between edox and warf at higher levels of renal function due to the preserved effect on bleeding and mortality (Fig 1b; p-int 0.17). An on-treatment analysis with plasma drug levels will be shown. Conclusion: While there is a trend towards decreasing efficacy with increasing CrCl for edox compared to well-managed warfarin, the overall safety and net clinical benefit of edox compared to warfarin is consistent across renal function groups.

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